All progressive renal disease is eventually associated with proteinuria. Qualitative and quantitative changes in protein excretion are empirically correlated with certain categories of renal disease. The present study aims to supply pertinent data relative to an understanding of how large molecules gain access to the tubular lumen, and how and to what extent they are reabsorbed. The experimental animal is the rat, studied in a restraining metabolism cage. Solid phase radio immunoassay is used for protein quantitative analysis. The experimental design includes: 1) Study of the effects of various protein concentrations in the serum and volume expansion upon proteinuria. 2) In vitro recovery and analysis of the specific protein content of the pinocytotic vacuole-lysosomal system in the proximal tubule responsible for reabsorption of an as yet unknown quantity of filtered solute, including large molecules. Correlation of data derived from these approaches should enable reasonable hypotheses to be developed concerning the movement of protein through the kidney.